We traced the development of neurologic impairment in 207 homosexual men (123 human immunodeficiency virus [HIV]-positive and 84 HIV-negative controls) over 4.5 years of follow-up. We applied generalized estimating equations to logistic regression analyses with repeated measures to examine the differences between HIV-positive and HIV-negative subjects with respect to the likelihood of developing six neurologic outcomes derived from a factor analysis, significant neurologic impairment (modified Kurtzke disability score of > or = 3), or significant neuropsychological impairment. We found that, over time, HIV-positive subjects were more likely to develop clinically significant extrapyramidal signs and frontal release signs than HIV-negative subjects. Controlling for age or education, as CD4 count declined, the odds of developing significant extrapyramidal signs, abnormalities in alternating movements, frontal release signs, and a Kurtzke score > or = 3 increased. HIV-positive subjects were almost five times as likely (odds ratio [OR], 4.6; 95% CI, 1.6 to 13.4) as HIV-negative subjects to stay the same or worsen neurologically on the next visit, and those with CD4 < or = 200 were 4.8 times as likely (OR, 4.8; 95% CI, 2.2 to 10.7) to maintain or worsen neurologically relative to those with higher CD4 counts. We conclude that neurologic impairment becomes increasingly apparent over time in HIV-infected men, especially in those with low CD4 counts.