Toxoplasmic encephalitis is associated with high mortality and morbidity and still presents a notable incidence in our setting. Neither the clinical symptoms nor radiological features are diagnostic of this disease; however, because of its frequency and clinical importance, specific treatment is begun whenever toxoplasmosis is suspected. In patients with negative serology, or who are receiving adequate prophylaxis, or who do not respond to 2 weeks of treatment, or who present radiological lesions suggestive of another illness, diagnosis should not be delayed, and brain biopsy should be considered as soon as possible. In these cases, SPECT with 201TI (sensitivity and specificity over 90-95% for lymphoma) and/or the PCR technique to detect T. gondii (sensitivity 50-65% and specificity 95-100%) or Epstein-Barr virus (sensitivity 70-80% and specificity 95% for lymphoma) can be very useful. The treatment of choice is pyrimethamine (100 mg the first day followed by 50 mg/day) and sulphadiazine (1-1.5 g/6 h) during 6-8 weeks. If the patient is allergic to sulfadiazine and cannot be desensitized the regimen of choice is pyrimethamine and clindamycin (600 mg/6 h), with similar efficacy. Clinical experience with other therapeutic alternatives is limited. Pyrimethamine can be associated with clarithromycin (0.5-1 g/12 h), azithromycin (1-1.5 g/day) atovaquone (750 mg/6 h), dapsone (100 mg/day) or doxycyclin (200 mg/12 h). Cotrimoxazole or clindamycin can be administered intravenously to patients who cannot receive enteral treatment. The toxicity of these therapeutic regimens is significant and treatment has to be suspended in 10-40% of cases. The interactions that can be produced with other drugs used to treat HIV-infected patients are generally of little clinical relevance.