Three male college students from Florida developed acute onsets of fever, chills, shortness of breath, and cough within one day of each other, and all were eventually hospitalized for four to 29 days. All chest x-ray films showed diffuse reticulonodularities in both lung fields. Laboratory studies confirmed the diagnosis of histoplasmosis. The three students had been 'spelunking' (cave exploring) 6 to 7 days before their onset of symptoms. One of four soil samples collected in the caves was positive for Histoplasma capsulatum by the indirect mouse inoculation procedure. Of three investigators who entered the implicated caves, two developed acute febrile illness within 15-21 days. One investigator was hospitalized for 18 days with a confirmed diagnosis of histoplasmosis. Investigation identified an additional case (the person had entered the caves 6 months before this episode), but was not reported to health authorities. Spelunkers should be aware of the potential risk of histoplasmosis and how to avoid infection. Physicians should be cognizant of cave-associated histoplasmosis, inquire about spelunking in persons who develop febrile respiratory illnesses with diffuse nodularities on chest x-ray films, and report such cases to their health department. A review of 42 reported outbreaks of cave-associated histoplasmosis and the approach to environmental control of infected caves are included.