Cyclophosphamide is widely used to induce a remission of minimal-change nephropathy, but concerns have been raised about whether its effects on cellular immunity persist after treatment is discontinued. We studied functional and numerical measures of cellular immunity in children who had minimal-change nephropathy with frequent steroid-responsive relapses and were receiving cyclophosphamide (2.5 mg per kilogram of body weight per day for eight weeks). Sequential studies during such treatment showed that cyclophosphamide caused lymphopenia, particularly among T helper cells, resulting in a significant fall in the immunoregulatory (helper/suppressor) cell ratio. This change persisted 1 to 3 months after cyclophosphamide was discontinued, but measures of immune function reverted to normal after 6 to 12 months. Children with minimal-change nephropathy in long-term remission had no difference in T-cell subpopulations, lymphocyte responses to mitogens, or suppressor-cell function that could be attributed to the disease itself or to the previous use of cyclophosphamide.