Between October 1998 and April 1999, 51 persons belonging to two separate groups developed acute pulmonary histoplasmosis after visiting a cave in Costa Rica. The first group consisted of 61 children and 14 adults from San Jose, Costa Rica; 44 (72%) were diagnosed with acute histoplasmosis. The second group comprised 14 tourists from the United States and Canada; 9 (64%) were diagnosed with histoplasmosis. After a median incubation time of 14 days, the most common symptoms were headache, fever, cough, and myalgias. Risk factors for developing histoplasmosis included crawling (odds ratio [OR] = 17.5, 95% confidence interval [CI] = 2.3–802) and visiting one specific room (OR = 3.4, 95% CI = 1.0–12.3) in the cave. Washing hands (OR = 0.1, 95% CI = 0.01–0.6) after exiting the cave was associated with a decreased risk of developing histoplasmosis. Histoplasma capsulatum was isolated from bat guano collected from inside the cave. Persons who explore caves, whether for recreation or science, should be aware of the risk bat-inhabited caves pose for developing histoplasmosis, especially if they are immunocompromised in any way.