Intraventricular administration of amphotericin B for meningitis due to Cryptococcus neoformans is usually reserved for selected, seriously ill patients with recurrent disease. Between September 1973 and November 1983, 10 of 23 patients treated for cryptococcal meningitis at Memorial Sloan-Kettering Cancer Center received intraventricular amphotericin B through subcutaneous reservoirs, in addition to systemic therapy. The value of intraventricular amphotericin B was assessed in the 13 patients treated for first episodes of meningitis with systemic amphotericin B and flucytosine. Death during therapy occurred in one of six patients with intraventricular and systemic therapy compared with six of seven patients with systemic therapy alone (p = 0.025). The cerebrospinal fluid was sterilized in six of six patients given systemic and intraventricular therapy compared with three of seven given systemic therapy alone (p = 0.049), and the cerebrospinal fluid cryptococcal antigen titer declined in six of six patients given systemic and intraventricular therapy compared with two of seven given systemic therapy alone (p = 0.016). In the 10 patients who received intraventricular therapy, there were no complications related to reservoir insertion; however, complications related to reservoir use requiring replacement or revision occurred in two patients, and bacterial infection occurred in one but was treated successfully without removal of the reservoir. Although these data are retrospective, they suggest that early therapy with intraventricular amphotericin B in combination with systemic therapy may be beneficial and relatively safe in patients with cryptococcal meningitis and a poor prognosis.