The effect of ginseng consumption on the risk of cancer was investigated by interviewing 905 pairs of cases and controls matched by age, sex, and date of admission to the Korea Cancer Center Hospital, Seoul, Korea. Of the 905 cases 562 (62%) had a history of ginseng intake compared to 674 of the 905 controls (75%) a statistically significant difference (p < 0.01). The odds ratio (OR) of cancer in relation to ginseng intake was 0.56 (95% confidence interval (Cl), 0.45-0.69). Ginseng extract and powder were shown to be more effective than fresh sliced ginseng, the juice, or tea in reducing the OR. Odds ratios for decreasing levels of ginseng intake were 1.00, 0.58, 0.43 and 0.25 for males and 1.00, 0.81, 0.56 and 0.52 for females. A trend test showed a significant decrease in proportion of cancer cases with increasing frequency of intake for males (p < 10(-5)) as well as for females (p < 0.05). Chi-square homogeneity tests also confirmed significant differences between cases and controls for both sexes (p < 10(-3)). The reliability of recall for ginseng use was assessed by interviewing 180 randomly-selected subjects twice using the same questionnaire. The overall agreement in reported ginseng use between the two interviews was 0.85, and the Kappa value was 0.71 (p < 0.01). These results strongly support the hypothesis of preventive effects of ginseng on cancer suggested by earlier animal studies.