Intramuscular (im) pentamidine isethionate can cause substantial local pain and inflammation at the injection site. This drug is being used more frequently in recent years to treat Pneumocystis pneumonia, particularly in patients with acquired immunodeficiency syndrome. Clinicians began administering it iv despite warnings that iv administration might cause severe hypotension. We investigated the safety of im and iv pentamidine, monitoring hemodynamics after each dose in 11 patients with intra-arterial lines. Results showed only a small (but statistically significant) fall in mean arterial pressure after both im and slow (60 min) iv administration. A concomitant decrease in pulse occurred, but no change in cardiac output, pulmonary capillary occlusion pressure or systemic vascular resistance was noted. These results suggest that it may be safe to infuse pentamidine slowly intravenously. This route is more comfortable to patients than im administration.