Injection of complete Freund's adjuvant into one paw of Holtzman rats induced an inflammatory response in the injected site (primary lesion) and from the 10th day on, severe polyarthritis developed (secondary lesions). In this susceptible strain, cyclophosphamide dose dependently reduced the intensity of the primary and secondary lesions. In contrast, in Buffalo rats, which are considered as resistant, cyclophosphamide in the dose of 25 mg/kg significantly potentiated the secondary lesions. Higher doses (200 and 300 mg/kg) also reduced the intensity of the lesions in this strain. Our data suggest that the development of adjuvant induced arthritis is controlled by a cyclophosphamide sensitive suppressor cell population.