In order to examine whether cyclosporine activity in submaxillary lymph nodes is dependent on sympathetic modulation, rats received a unilateral superior cervical ganglionectomy together with a contralateral sham-operation. Two weeks later, cyclosporine (5 or 20 mg/kg per day s.c.) was injected for five days. Freund's complete adjuvant was injected 1 h before the third injection of cyclosporine and the rats were killed 2 h after the last injection of cyclosporine. A significant increase in ornithine decarboxylase activity in submaxillary lymph nodes was observed two weeks after sympathetic denervation. Cyclosporine decreased enzyme activity in submaxillary lymph nodes on the sham-operated side by 67-77% and by 21-41% on the denervated side (P less than 0.01). The incorporation of [35S]methionine into proteins in ipsilateral submaxillary lymph nodes was increased by unilateral superior cervical ganglionectomy and decreased by cyclosporine to a similar extent in denervated and innervated lymph nodes. Superior cervical ganglionectomy decreased by about 93-95% the norepinephrine content of submaxillary lymph nodes regardless of cyclosporine treatment. The results indicate that an appropriate sympathetic neural environment is needed for cyclosporine to have an effect on ornithine decarboxylase activity in lymphoid tissue.