We reviewed the clinical features and risk factors for Pneumocystis carinii pneumonia (PCP) in patients with brain tumors (BTs) seen at our institution between 1980 and 1992. Previously rare, this opportunistic infection appears to be increasing among HIV-negative cancer patients receiving immunosuppressive medications. Recent reports have noted PCP among BT patients receiving corticosteroids, and suggested that these patients are particularly likely to develop PCP when corticosteroids are tapered. Nine BT patients, eight with high-grade gliomas, experienced ten episodes of PCP. None were known HIV-positive. All were on dexamethasone (DXM) at PCP onset, and had continuously been receiving it for 47-398 days (median 69). Daily DXM dose at PCP onset ranged from 1-16 mg (median 9). Five episodes occurred in patients receiving a stable DXM dose and five during DXM taper. Nine episodes occurred in patients receiving chemotherapy. All patients had absolute lymphopenia at PCP onset, ranging from 80-900 x 10(6) lymphocytes/l (median 222 x 10(6)/l, normal > 1000 x 10(6). Three episodes were fatal despite appropriate antibiotic therapy. Unlike others, we did not find that corticosteroid taper predisposed to developing PCP. As in HIV, PCP in BT patients appears related to lymphopenia, in these patients attributable to use and duration of corticosteroids and in some cases cytotoxic chemotherapy. Effective prophylaxis exists and should be considered for lymphopenic patients and those requiring DXM for > five weeks.