OBJECTIVE To determine the efficacy of calcium supplementation in women with premenstrual syndrome (PMS). METHODS Randomized, double-blind crossover trial. METHODS Outpatient medical clinic of a large city hospital. METHODS Seventy-eight women were initially screened. Trial selection was based on a history of recurrent PMS symptoms and on the results of a prospective assessment of daily symptom scores. Only women with symptom scores during the late luteal phase that were at least 50% greater than those during the intermenstrual phase were selected. Thirty-three women completed the trial. METHODS A preliminary evaluation included physical examination, routine laboratory tests, dietary assessment, and psychiatric evaluation. Each participant received six months of treatment involving three months of daily calcium supplementation (1,000 mg of calcium carbonate) and three months of placebo. METHODS Efficacy was assessed prospectively by changes in daily symptom scores over a six-month period and retrospectively by an overall global assessment. Multivariate repeated measures analysis of variance on symptom ratings derived from daily PMS symptom scores demonstrated a reduction in symptoms on calcium treatment during both the luteal (p = 0.011) and the menstrual phases (p = 0.032) of the reproductive cycle. Calcium supplementation had no effect during the intermenstrual phase. Retrospective assessment of overall symptoms confirmed this reduction: 73% of the women reported fewer symptoms during the treatment phase on calcium, 15% preferred placebo, and 12% had no clear preference. Three premenstrual factors (negative affect [p = 0.045]; water retention [p = 0.003]; pain [p = 0.036]) and one menstrual factor (pain [p = 0.02]) were significantly alleviated by calcium. CONCLUSIONS Calcium supplementation is a simple and effective treatment for premenstrual syndrome, but further studies will be needed to determine its precise role in PMS.