The information-motivation-behavioral skills (IMB) model (Fisher & Fisher, 1992) was used as the theoretical framework for predicting unprotected sexual behavior among substance abusing men and women diagnosed with serious mental illnesses (n = 320; 150 men and 170 women, primarily of minority ethnicity). In a structural equation model, gender, HIV transmission knowledge, and motivational variables of pro-condom norms and attitudes, and perceived susceptibility predicted behavioral skills markers: condom use skills and condom use self-efficacy. Along with the other variables in the model, condom skills and condom self-efficacy were hypothesized to predict condom use over a six-month period. Results showed that greater condom skills were predicted by female gender, positive condom attitudes, and transmission knowledge. Engaging in lower rates of unprotected sex was predicted by pro-condom norms, less perceived susceptibility, and greater condom self-efficacy. Positive attitudes toward condoms had a significant indirect effect on rates of unprotected sex, exerting its influence through condom use self-efficacy. Results suggest that changing personal attitudes about condoms and reinforcing pro-condom attitudes among significant others will encourage condom use among seriously mentally ill (SMI) adults who are at high risk for HIV and other sexually transmitted diseases (STDs).