Glioma often recurs after apparently successful treatment and clinical remission. The effect of the host's immunologic status in such cases is unknown. In this study, the authors attempted to answer the following questions: 1) Is there a relationship between immunity and the recurrence of glioma? 2) Is immunologic monitoring useful in predicting the recurrence of glioma? 3) Which immunologic monitoring system is the most reliable? The subjects were 17 patients with gliomas who were treated between 1980 and 1985 and had tumor recurrence after an interval of clinical remission. They were evaluated during and after remission by means of clinical signs, computed tomography, and immunologic testing, which included measurement of purified protein derivative (PPD), phytohemagglutinin (PHA), the blastogenic response of T-lymphocytes to PHA, the OKT4 and OKT8 lymphocyte subsets, and serum complement CH50. The patients were divided into two groups. Group 1 comprised five patients whose tumors showed malignant transformation from grade 2 to grade 3. Group 2 included patients whose tumors were of the same histologic grade initially and on recurrence. In Group 2, six tumors were grade 3 and six were grade 4. Lowered immunity at the time of recurrence was demonstrated by the following: 1) a negative change in PPD and/or the PHA skin reaction in 80% of Group 1 and 75% of Group 2 patients; 2) elevation of CH50 in 40% of Group 1 and 58% of Group 2 patients; 3) a change in the blastogenic response of T-lymphocytes to PHA in 40% of Group 1 and 25% of Group 2 patients; and 4) an decrease in OKT4/OKT8 cell ratio in 60% of Group 1 and 38% of Group 2 patients. These patients were immunologically competent during remission. The immunologic changes at the time of tumor recurrence were accompanied by clinical deterioration. However, tumor recurrence could not be predicted from the immunologic parameters studied. Thus, it appears that extension or recurrence of the gliomas was responsible for lowered immunity in these patients, rather than the opposite.