A total of 95 patients who presented in 1994 and 1995 with focal brain lesions at a London HIV centre were studied retrospectively.Patients were allocated to 'definite' or 'presumed' diagnostic categories of toxoplasma encephalitis (TE), primary CNS lymphoma (PCNSL) or progressive multifocal leuko-encephalopathy (PML), based on strict criteria. The number in each category was: TE, 20; PCNSL, 9; PML, 7; presumed TE, 12; presumed PCNSL, 8 and presumed PML, 17. There were 20 patients in whom a diagnosis could not be made, and there were three non-HIV diagnoses. Demographic data, features at presentation and routine CSF analysis were not discriminatory in making a diagnosis. Toxoplasma titres were a median of 1 : 256 in those with TE compared to 1 : 16 in all other groups (p < 0.001) and those with TE were less likely to be on toxoplasma prophylaxis compared to those with PCNSL (p < 0.002). Survival with TE (median of 446 days) was significantly longer than survival in all other groups. Survival with either confirmed or presumed PML was similar. The problems of diagnosis of focal brain lesions in HIV patients are discussed and a management flow chart for mass lesions is proposed.