Cryptococcus neoformans (Cn) is a frequent pathogen in patients infected with the human immunodeficiency virus (HIV-1). We review the initial presentation and clinical course of 18 HIV-1-infected (HIV+) patients with a Cn pulmonary infection. Simultaneous positive cerebrospinal fluid (CSF) cultures were found in 10 (63%) of 16 examined. The most frequent presenting symptoms were fever (87%) and pulmonary complaints (60%). Although the most common chest radiographic finding was bilateral diffuse interstitial infiltrates, nodules and cavitary lesions were also seen. Nine (50%) of the 18 patients died within 6 weeks of diagnosis. Of six patients with an isolated Cn pulmonary infection, five have subsequently died. Three of these five patients did not receive maintenance therapy and had confirmed or probable relapse. Patients initially presenting with an isolated Cn pulmonary infection may later show disseminated disease, suggesting that such patients should receive both acute and maintenance therapy.