Nurses play a major role in the health care delivery system; therefore, education of nurses is critical to successful prevention programs for persons with HIV. Little is known about nurses' knowledge of HIV in India. The purpose of this study was to determine the effects of a nurse-led train-the-trainer HIV education program on improving the HIV knowledge of nurses. A group of senior nurses (N = 10), were responsible for training a cohort of 10 nurses each, totaling 100 nurses. The 2-day training program included HIV epidemiology and etiology, infection control, psychosocial support, counseling, modes of transmission, natural history of the disease, symptoms of early and late disease, diagnostic testing, and legal and ethical issues. Pre- and posttest scores were calculated using a self-administered structured questionnaire that measured HIV-related knowledge in terms of cognitive and transmission knowledge. Paired t-tests indicated that both measures of HIV knowledge improved significantly from pretest to posttest.