Cyclic 3',5'-adenosine monophosphate (cAMP) and cyclic 3',5' guanosine monophosphate (cGMP) may influence important regulatory mechanisms in the rheumatoid inflammatory process. It has been claimed that fasting improves the condition of the patient with rheumatoid arthritis (RA). The present study was designed to measure cAMP in plasma and urine cGMP in urine in medically untreated RA patients. 12 female patients were investigated in a cross-over study during a control and a fasting period. They received no other drugs than analgesics during these periods. Levels of plasma and urinary cAMP found during the control period were somewhat lower than previously reported. However, the ratio cAMP/cGMP in urine was 10 to 1 which is reported to be normal. Clinical and laboratory variables of inflammatory activity were significantly improved during the 7-day fasting period. The ratio of cAMP/cGMP in urine was significantly increased on days 2-4 and coincided in time with the maximum of clinical improvement. Cyclic AMP concentrations were lowered both in plasma and urine during fasting. This is in contrast to fasting in normal and obese subjects reported in previous studies.