Lipopolysaccharide (LPS)- and concanavalin A (ConA)-induced proliferation and T lymphocyte subsets were measured in spleen and submaxillary lymph nodes of male rats injected with cyclosporine (5 mg/kg s.c. for 5 days, at 12.00 or 24.00 h; animals kept under light from 08.00 to 20.00 h daily). One hour before the third injection, Freund’s complete adjuvant or its vehicle was administered. A suppressive effect of cyclosporine on the mitogenic action of LPS was seen in the spleen of rats injected with cyclosporine at noon whereas the effect of ConA remained unaffected. CD4+, CD8+ and CD4+-CD8+ cells decreased in spleen and lymph nodes of Freund’s adjuvant-injected rats only with cyclosporine given at noon. The results further support occurrence of time-of-day-dependent effects of cyclosporine on lymphocyte subsets and proliferation.