Persistent eosinophilia in humans is often associated with endocardial damage to the heart, but a causal relation has not been established. We investigated the effect of eosinophils and eosinophil supernatants obtained from eight hypereosinophilic patients on the contractile performance and endocardial morphology of isolated, electrically stimulated cat papillary muscle preparations (n = 16). All these eosinophil suspensions contained high proportions of "hypodense" or "activated" cells. Eosinophils (5-15 x 10(6) ml organ bath) or eosinophil culture supernatants (prepared by overnight incubation at 37 degrees C) when added to papillary muscles produced acute changes in contractile behavior of these muscles identical to the previously reported effects of selective endocardial damage: a reduction in time to peak isometric twitch tension causing a reduction in peak isometric tension but with no significant reduction in rate of tension development or in maximum unloaded shortening velocity. All of these muscle preparations showed severely damaged endocardium at scanning electron microscopy. Addition of eosinophils from hypereosinophilic patients to muscles with selectively damaged endocardium (by previous transient [1-second] exposure to 1% Triton X-100) produced no further change in contractile performance. No significant change in contractile performance or endocardial morphology of papillary muscles (n = 16) was observed after addition of eosinophils (7.5-10 x 10(6] or neutrophils (8-15 x 10(6] from normal subjects or of cell-free culture medium. Thus, activated human eosinophils produce specific morphological and functional changes suggestive of specific damage to endocardium of isolated feline cardiac muscle.