Graves' disease (GD) is an autoimmune thyroid disease characterized among other findings by diffuse goiter. It is possible in GD to find a multinodular goiter (mGD). Are they two different diseases that coexist, or do we have a multinodular type of GD. Questions arise as for the time that this mGD appears in the process of GD and also, as for the clinical and laboratory characteristics of mGD. To answer these questions, we have studied retrospectively and randomly from the archives of the Department of Nuclear Medicine of AHEPA University Hospital, from 2000-2004, 20 female patients with multinodular type of GD (Group A) as first diagnosed by us and 50 female patients with diffuse type of GD (Group B) of about the same age. Patients with mGD had been examined before by us and their GD was documented. No other cause for exophthalmus except GD was found. Patients with any other additional disease were excluded from the study. All patients had 7-10 signs of hyperthyroidism (thyroid index). Many of the patients, after the present study, were given (131)I therapeutically. These groups were divided in subgroups of pre- and menopausal women (A1, B1 and A2, B2 respectively). The mean age of our patients in Groups A and B were 46 and 50 years with a range of 25-65 and 38-69 years respectively. Serum free triodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), thyroid peroxidase antibodies (AbTPO), antithyroglobulin antibodies (AbTG) and anti receptors of thyroid stimulating hormone antibodies (AbTSHR) were tested in all subjects studied by radioimmunoassays (RIA) or radioimmunometric assays (IRMA). All patients were under antithyroid treatment interrupted for about 10 days before the thyroid scan. Thyroid scintiscan was performed 24 h after oral intake of 1.8 MBq of (131)I. Clinical findings were evaluated by a clinical index of hyperthyroidism as modified by us. The time that the mGD appeared since the beginning of GD and the time the GD started were also studied. Our findings were as follows: A mean time of 10.35+/-6.7 years had elapsed from the start of GD till mGD was first diagnosed by us. A mean time of 3.1+/-1.6 years had elapsed after the start of the GD till patients of Group B were examined in this study. No difference in the values of FT3, FT4 and TSH between the two Groups or the Subgroups was found as expected because the clinical status of the patients varied. AbTG, AbTPO and AbTSHR were found in a much higher incidence and in higher values in Group A versus Group B (P=0.007 and 0.001 respectively) and in Subgroups A1, A2 versus B1 and B2 respectively. This increase was significant for AbTG and AbTPO in A2 versus B2 Subgroups and for AbTPO in A1 versus B1 Subgroups (P=0.007, 0.001 and 0.014 respectively). We were unable to find a similar work in the literature. In conclusion, we suggest that mGD as compared to GD: a)develops late in GD and thus patients had more relapses, b) has a higher incidence of abnormal values of AbTPO, AbTG and AbTSHR, c) has significantly higher values of AbTPO and less of AbTG than GD and d) thyroid hormones, clinical index of hyperthyroidism and the incidence of exophthalmos do not differ. Based on the above, we suggest that mGD is a late evolutionary type of GD. The study of patients of both sexes having GD of the same duration as mGD, the study of iodine metabolism and of thyroid gland pathology in these patients, is needed.