Three groups of rats were fed a low-sodium diet. Groups 1 drank water and was treated with cyclosporine, 100 mg kg-1 48 h-1 p.o. for 3 weeks (low-salt-treated group). Group 2 drank 0.15 M saline and was also treated with cyclosporine (high-salt-treated group). Group 3 drank water and was treated with the vehicle (low-salt-vehicle group). Measurements were made during a control period and weekly during the 3-week treatment period and a 3-week recovery period. Both cyclosporine-treated groups lost weight during treatment but the rises in serum creatinine and blood urea and decrease in creatinine clearance were greater in the low-salt group. The vehicle group gained weight and had no change in the other parameters over the three weeks. There was an increase in urine volume and sodium excretion in the high-salt group associated with cyclosporine treatment. Although the low-salt groups had a higher plasma renin concentration than the high-salt group there were no changes produced by cyclosporine treatment. Histopathological examination showed mild tubular lesions with vacuolar degeneration of proximal tubular cells. This was more prevalent in the low-salt-cyclosporine-treated group. The plasma concentrations of cyclosporine were not different after one-week treatment but were slightly greater after 2 week and 3-week treatment in the low-salt group. We have suggested that the greater impairment of renal function in the low-salt group produced by cyclosporine may be contributed to by an involvement of tubuloglomerular feedback.