We prospectively evaluated 94 patients with AIDS-dementia complex (ADC) and a smaller group of 27 patients with other HIV-1 related neurological conditions to determine the usefulness of cerebrospinal fluid (CSF) p24 antigen and HIV-1 culture in the diagnosis of ADC. The presence of ADC correlated with detectable CSF p24, but not with a positive culture. However, only 54% of the patients with severe or end stage (stages 3 and 4) ADC had detectable CSF p24 and only 25% had a positive culture. Among those with detectable CSF p24, there was no discernible relationship between the severity of ADC and the amount of CSF p24. The diagnostic sensitivity of CSF p24 in ADC was 21% whereas the specificity was 98%. CSF HIV-1 culture had a sensitivity of 30% and a specificity of 80%. To address the possibility of binding of p24 in immune complexes, thereby escaping detection, an acid hydrolysis procedure was performed on the CSF and serum samples. This did not, however, make an appreciable difference in the detection rate of p24. To delineate whether the finding of cell free virus in the CSF was associated with ADC, CSF culture for HIV-1 was performed on both cell depleted and cell associated fractions. It was uncommon for CSF to be culture positive in only the cell free fraction and there was no relationship to the presence or severity of ADC.