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In a multicenter cooperative study the effectiveness and side-effects of two most widely used regimens for prolonged interrupted prednisone treatment were compared in children with frequently relapsing nephrotic syndrome: i.e., alternate-day prednisone vs. intermittent prednisone. Sixty-four children were admitted to the study, 30 of whom were allocated to an alternate-day, 34 to an intermittent group. Sixteen patients did not complete the full trial, which left 48 children for final evaluation (23 alternate-day, 25 intermittent). The protocol consisted of two 6-month periods. During the first 6 months patients received maintenance prednisone (alternate-day = 35 mg/m/48 h, intermittent = 40 mg/m on 3 out of 7 days). During the second 6-month pericd no maintenance prednisone was administered unless a relapse occurred and was treated with a short course of prednisone. The alternate-day prednisone reduced the number of relapsers and the rate of relapses significantly as compared with the control period of the second 6 months. The intermittent prednisone, however, did not significantly lower the number of relapsers, but only the rate of relapses. In the alternate-day group the number of relapsers and the rate of relapses were significantly lower than in the intermittent group. Observation for toxic side-effects did not reveal any difference. It is concluded that an alternate-day regimen is preferable to the intermittent regimen, which should be abandoned in the treatment of children with the nephrotic syndrome. [ABSTRACT FROM AUTHOR]