Extracellular proteases from Pseudomonas aeruginosa play important roles in infections in the respiratory tract. The effect of erythromycin (EM), a macrolide antibiotic, on the production of elastase by P. aeruginosa was investigated in vitro and compared with the effect of other antibiotics. Thirty-four (94.4%) of thirty-six different strains produced detectable amounts of elastase determined by the gel diffusion method. The elastase production was inhibited completely by EM in 27 (79.4%) of 34 strains at some concentrations between 0.125 and 64 micrograms/ml. At 4 micrograms/ml or less, the elastase production was inhibited completely in four (11.8%) strains and more than 50% in the other 10 (29.4%). At 8 micrograms/ml or less, the elastase production was inhibited completely in 11 (32.4%) strains and more than 50% in the other nine (26.5%). The proliferation was partially inhibited at 32 and 64 micrograms/ml. Roxithromycin inhibited the elastase production at higher concentrations than EM without inhibiting the proliferation. Midecamycin and ampicillin did not inhibit the elastase production or the proliferation. Doxycycline and ticarcillin inhibited the elastase production and/or the proliferation at concentrations greater than 16 micrograms/ml. Although ofloxacin (OFLX) inhibited both the proliferation and the elastase production in parallel at low concentrations, there were six (16.7%) strains resistant to OFLX. Among them the elastase production was inhibited in five strains by EM. These results suggest that EM acts on P. aeruginosa to inhibit extracellular production of elastase without affecting the proliferation of the bacteria.