Cyclic adenosine-3', 5'-monophosphate (cAMP) may influence important mechanisms in the inflammatory process, and fasting has been claimed to be clinically beneficial in rheumatoid arthritis (RA). A study was therefore designed to measure the concentrations of plasma cAMP in RA patients not undergoing drug treatment during a control and a fasting period. Twelve female RA patients were hospitalized for two 14-day periods and investigated in a crossover study. Clinical and laboratory variables of inflammatory activity were assessed during both periods. During the control period the concentrations of cAMP in plasma were slightly below the lower normal limit, with no significant change throughout the period. The clinical and laboratory variables of inflammatory activity were unchanged during the same period. In the fasting period, the prefasting level of plasma cAMP was significantly higher than on the corresponding day in the control period. During 7 days of total fasting the plasma cAMP concentrations decreased significantly. The clinical and laboratory variables of inflammatory activity decreased significantly from the start to the end of fasting. High prefasting plasma cAMP concentrations were associated with improvement in clinical inflammatory activity. A decrease in plasma cAMP concentrations during fasting in RA patients is in contrast to the findings in obese and healthy subjects previously reported.