Between December 1972 and February 1973, 2349 volunteers participated in a double-blind trial to assess the effect of large doses of vitamin C on the incidence and severity of winter illness. In addition, records were kept but no tablets taken during March. Subjects were randomly allocated to eight treatment regimens: three prophylactic-only (daily dose 0.25, 1 or 2 g), two therapeutic-only (4 or 8 g on the first day of illness), one combination (1 g daily and 4 g on the first day of illness), and two all-placebo. None of the groups receiving vitamin C showed a difference in sickness experience that was statistically significant from that of the placebo groups, but the results obtained were compatible with an effect of small magnitude from both the prophylactic and therapeutic regimens, and an effect of somewhat greater magnitude from the combination regimen. The combination regimen was associated more with a reduction in severity than frequency of illness, although the extra dosage was limited to the first day of illness. In spite of the eightfold range in daily dose, the three prophylactic-only regimens showed no evidence of a dose-related effect, but the 8 g therapeutic dose was associated with less illness than the 4 g therapeutic dose. There was no evidence of side effects from the 1 and 2 g prophylactic doses of vitamin C, and no evidence of a rebound increase in illness during the month following withdrawal of the daily vitamin supplements. On the basis of this and other studies it is suggested that the optimum daily dose of vitamin C is less than 250 mg, except possibly at the time of acute illness, when a larger daily intake may be beneficial.