Paired sera from victims of Legionnaires' disease showed, in many cases, significant rises in immunoglobulin G antibodies to both the causative agent (LA) of Legionnaires' disease and Chlamydia psittaci, but concurrent rises in immunoglobulin M antibodies only against LA. Guinea pigs experimentally infected with LA likewise responded with antibodies to both C. psittaci and LA. Guinea pigs infected with LA also reflected significant differences in antigenic makeup and in pathogenicity among four strains of LA examined. In antibiotic studies, rifampin was 200 times more effective than erythromycin and 17,000 times more effective than tetracycline in plaque reduction tests of LA in monolayer cultures of primary chick embryo cells. An isolate of LA recovered from a healthy person was compared with three isolates from persons with fatal infections.