Objective: To determine whether or not soluble factors produced by peripheral blood mononulear cells (PBMC) can predict AIDS dementia. Design and methods: PBMC were isolated from individuals with and without AIDS dementia complex (ADC) to determine if the levels of cytokines tumour necrosis factor (TNF)-α and interleukin (IL)-6, or the production of a neurotoxic substance, were significantly different. PBMC were studied after determining that the numbers of monocyte-derived macrophages isolated by adherence were highly variable from patients with ADC compared with individuals without ADC. We prospectively studied 16 AIDS dementia patients, 13 healthy HIV-seropositive individuals, and eight seronegative controls. Supernatants from PBMC were assayed for TNF-α, IL-6 and alone for neurotoxicity on human neural cells in vitro. Results: We observed a trend towards worse cognitive and motor performance in patients suffering from ADC but who had no opportunistic infections (‘pure dementia’; n = 8). Levels of PBMC IL-6 were significantly higher in ‘pure dementia’ patients. There was a trend towards lower levels of PBMC TNF-α in the group of patients who had both dementia and opportunistic infections compared with ‘pure dementia’ patients. Supernatant from PBMC of ADC patients was significantly more neurotoxic than that from healthy HIV-seropositive individuals. Conclusions: Macrophage isolation from PBMC of patients with ADC was altered. Soluble factors produced from PBMC were significantly more neurotoxic than soluble factors from PBMC of healthy HIV-seropositive individuals. PBMC production of TNF-α and IL-6 was not a significant predictor of ADC.