Seventy-five consecutive clinical Pseudomonas aeruginosa isolates were tested for in vitro exotoxin production. Exotoxin was demonstrated in culture filtrates biologically, by its ability to produce characteristic dermonecrotic lesions in guinea pigs, and seriologically, by counterimmunoelectrophoresis (CIE) with rabbit antiserum elicited with purified exotoxin. By these two methods, exotoxin was detected in 87 and 89% of P. aeruginosa strains, respectively (r = 0.48, P less than 0.001). Although less sensitive than CIE in detecting exotoxin immunodiffusion demonstrated a reaction of antigenic identity in most cases. Exotoxin was produced by all seven Fisher-Devlin immunotypes and by untypable strains. In contrast, exotoxin was not detected in the culture filtrates of 16 non-aeruginosa pseudomonas isolates and 48 non-pseudomonas organisms. The production of biologically similar antigenically closely related exotoxins is thus a characteristic of the majority of P. aeruginosa strains derived from diverse clinical sources.