Cyclosporin A (CsA) was administered s.c. to BALB/c and C3H mice for periods up to 25 days and the effects were monitored by the immune response to SRBC, HGG, and B. abortus. Whereas the rate of growth of BALB/c mice was only depressed after the 20th day, C3H mice lost weight from the start of treatment. In both strains there was no change in the weight of the spleen and mesenteric lymph node but the thymus weight decreased markedly. This decrease in thymus weight was accompanied by thymic involution with little or no change in spleen or mesenteric lymph node. An increase in Mott cells, as so strikingly demonstrated in the CsA-treated chicken (Nowak et al., 1982), was dependent on the degree of thymic involution. When the thymus was normal in appearance there was a slight increase in the number of splenic Mott cells, when compared with untreated controls; in the more usual case of thymic involution (or necrosis), there was no increase in the number of Mott cells.