The growth of Pseudomonas aeruginosa, particularly serotype O11, in pentazocine and tripelennamine ("T's and Blues") was evaluated as a possible explanation for the association of deep-seated infection with this organism and abuse of these drugs. The mean reduction of growth caused by the drugs was 1,000-fold greater for 49 Pseudomonas strains from normal subjects than for 32 strains from drug addicts (4.2 vs. 1.3 logs of reduction at 2 hr, P less than .0005). A common phenotypic subset of the serotype O11 strains from drug addicts was especially resistant to the inhibitory effects. Twelve strains of Staphylococcus aureus (a frequent cause of infection in heroin, but not in pentazocine and tripelennamine, addicts) were completely inhibited by the drug combination. Dose-response curves (derived from the results of using the tablets as well as pure powders) showed that tripelennamine was responsible for the inhibitory activity, which was partially antagonized by pentazocine. We conclude that an ability of some P. aeruginosa serotype O11 strains, but not S. aureus, to survive in pentazocine and tripelennamine may explain in part a shift from S. aureus to P. aeruginosa as common pathogens of drug addicts in areas where abuse of this combination of drugs has increased.