Preliminary studies suggested that mycophenolate mofetil (MMF), which inhibits proliferation of T and B cells, may reduce the frequency of acute rejection after renal transplantation. Our randomised, double-blind, multicentre, placebo-controlled study compared the efficacy and safety of MMF with placebo for prevention of acute rejection episodes after first or second cadaveric renal allograft transplantation. 491 patients were enrolled; 166 were assigned placebo, 165 MMF 2 g, and 160 MMF 3 g. Patients also received cyclosporin and corticosteroids. Significantly fewer (p < or = 0.001) patients had biopsy-proven rejection or withdrew early from the trial (for any reason) during the first 6 months after transplantation with MMF 2 g (30.3%) or 3 g (38.8%) than with placebo (56.0%). The corresponding percentages for biopsy-proven rejection were 17.0%, 13.8%, and 46.4%. 28.5% of MMF 2 g and 24.4% of MMF 3 g patients needed full courses of corticosteroids or antilymphocyte agents for treatment of rejection episodes in the first 6 months, compared with 51.8% of placebo recipients. By 6 months, 10.2%, 6.7%, and 8.8% of the patients in the placebo, MMF 2 g, and MMF 3 g groups, respectively, had died or lost the graft. Overall, the frequency of adverse events was similar in all treatment groups, although gastrointestinal problems, leucopenia, and opportunistic infections were more common in the MMF groups and there was a trend for more events in the 3 g than the 2 g group. MMF significantly reduced the rate of biopsy-proven rejection or other treatment failure during the first 6 months after transplantation and was well tolerated. The 3 g dose was somewhat less well tolerated.