Although research on masculinity and femininity has increased over the past decade, longitudinal studies addressing predictive elements are lacking. The Rush Medical College Longitudinal Study examines the correlation between masculinity and femininity on the one hand and adjustment, interpersonal functioning, and impairment on the other. During orientation, 67 male and 32 female first-year medical students completed the Personality Attributes Questionnaire and 21 months later also completed measures of psychological well-being, interpersonal functioning, humanistic attitudes toward patient care, and alcohol consumption. Hierarchical multiple regression analyses with interaction terms revealed main effects of masculinity on self-esteem, extroversion, and confidence, and main effects of femininity on hedonic capacity, interpersonal satisfaction, sharing of personal problems, and alcohol consumption. Measures of impaired mood and alcohol and drug impairment were also studied in relation to masculinity and femininity. Both variables contributed to the prediction of depressed mood; femininity also contributed to the prediction of drug impairment. Neither scale has sufficient sensitivity or specificity to be used by itself as a test of impairment. Further study is needed to measure the precise relationship among low femininity, low hedonic capacity, and high potential for substance abuse. (Six data tables are included.) (Author/TW)