We evaluated the clinical and imaging features of cranial toxoplasmosis in patients without HIV infection. Between 1995 and 2005, 15 patients with serologically proven cranial toxoplasmosis were selected for clinical and imaging study from 233 patients with chronic meningitis and 364 patients with seizures/psychosis. All patients had poor immune status due to nutritional and metabolic causes. Neurological presentations included focal encephalitis, multifocal encephalitis and diffuse meningoencephalitis. The three groups had distinct symptoms and imaging features, with some overlap. Magnetic resonance imaging showed single or multiple nodular or ring-enhancing lesions often at the grey-white junction with subcortical white matter perifocal oedema. Within the large diffuse lesions there were discrete small haemorrhagic lesions and contrast medium administration showed fine-beaded parallel lines or small discrete nodules traversing the white matter suggesting perivenous spread. Complete clinical recovery was noted in 12 patients after several 6-week courses of pyrimethamine and sulfonamide/clindamycin. Five patients required two such courses, three patients required three courses, three patients required five courses and two patients required six courses for the final radiological healing, which was complete in nine patients. One patient was lost to follow-up and one patient died of cardiomyopathy. Knowledge of these three distinct initial presentations may help in the early diagnosis of cranial toxoplasmosis in HIV-seronegative patients. Prognosis in early cases is generally good but complete recovery may need several courses of treatment.