An analysis was made of the clinical course of 218 steroid-responsive children with minimal change nephrotic syndrome during the two-year period following initial response to prednisone therapy. No correlation was found between the frequency of relapse and (1) the histopathologic subgroups of minimal change nephrotic syndrome, (2) clinical or laboratory characteristics observable at the time of diagnosis, (3) the time of initial response, or (4) the interval between the initial response and the first relapse. The number of relapses that occurred during the first six months was highly predictive of the subsequent course. Of 99 children who had no relapse during this period, 93 had fewer than three during the subsequent 18 months, and only one had more than six. In contrast, among 37 who had three or more relapses in the first six months, 17 had more than six, 13 had 10 or more, and only seven had fewer than three relapses. The course of children who had either one or two relapses during the first six-month period was intermediate. These results provide substantial data for predicting the clinical course of minimal change nephrotic syndrome during the first two years and will help in preparing children and their families to anticipate the likely course of disease. The data should be useful also in selecting potential frequent relapsers for clinical trials.