The effects of the chlordane-related compounds, cis-chlordane, trans-chlordane, heptachlor, and heptachlor epoxide, on stimulation responses of guinea pig polymorphonuclear leukocytes (PMNs) were examined. Treatment of PMN with these compounds stimulated superoxide (O2-) generation, altered membrane potential, and increased intracellular Ca2+ concentration ([Ca2+]i). However, there was no definite tendency among the stimulating effects of chlordane-related compounds, therefore the relationship between the effect and molecular structure of these substances remains unknown. Of these response reactions of PMN stimulated by chlordane-related compounds, stimulation of O2- generation lagged behind others. Increase in [Ca2+]i was due both to acceleration of extracellular Ca2+ penetration and to Ca2+ release from the intracellular pool. These results indicate that chlordane-related compounds stimulate PMN and suggest a causal relationship between the stimulation of O2- generation by these substances and their toxicity.