The effect of cyclosporin A (CSA) on the antibody response to pneumococcal polysaccharide type III (a T-independent class 2 antigen) was investigated in mice. A single oral CSA administration (50 mg/kg) was able to depress (40%) the primary antibody response evaluated as spleen plaque-forming cells. Repeated treatments (12-50 mg/kg x 5) resulted in a higher degree of inhibition (80%) of anti-SIII response. Both single and repeated CSA treatments were active only when administered concomitantly with or after immunization, whereas no effects were seen with drug pretreatment. Comparable inhibitions of anti-SIII response were observed in control and nude mice suggesting a direct effect of CSA on B-cells.