We tested the hypothesis that symptomatic infection with Paracoccidioides brasiliensis caused impaired host cellular immune responses. In a cross-sectional study in Colombia, the immune responses of thirty-six patients with paracoccidioidomycosis were compared with those of sixty normal individuals. Patients demonstrated increased skin sensitivity to paracoccidioidin (para) and histoplasmin, and reduced reactivity to candidin and dinitrochlorobenzene as compared to controls. The skin test response to tuberculin (PPD) was similar to that of controls. In vitro lymphocyte transformation (LT) and leucocyte migration responses to phytohaemagglutinin and PPD did not differ in patients and controls; these responses to PPD correlated with skin sensitivity in controls, but not in patients. LT and inhibition of leucocyte migration to para were seen in more patients than controls; the latter response correlated with skin sensitivity in controls only. Positive LT to para was associated with absence of antibodies to P. brasiliensis. Analysis of symptomatic patients suggests that the prevalence of para skin test positivity was lowest in patients with the longest duration of disease; this implies decrease in specific cell-mediated immunity with prolonged active infection. Analysis of clinically cured patients suggests that the prevalence of para skin sensitivity and LT to para and PPD increased with time elapsed since diagnosis; this implies development or restoration of immunocompetence upon clinical recovery. Results of a preliminary longitudinal study on the immunological responses of six patients with active paracoccidioidomycosis are compatible with the above observations.