Recent experimental evidence implies that polyunsaturated fatty acids (PUFAs) possess anti-infective activity which is unrelated to any alteration of eicosanoid biosynthesis or cytokine production provoked by PUFAs and it seems necessary to establish their possible influence on Gram-negative bacteria. Forty-two Escherichia coli strains were cultured in vitro in the presence of gamma-linolenic acid (GLA) at concentrations of 50 mg/L and 300 mg/L and a total of 77 killing curves were performed with GLA concentrations of 100, 200 and 300 mg/L GLA. At 50 and 300 mg/L, GLA inhibited 9.5% and 33.3% of strains respectively; GLA killing curves demonstrated a > or = 1 log GLA inhibitory effect in 0%, 18.2% and 72.7% of strains after the 5 h sequential exposures at 100, 200 and 300 mg/L GLA but this was not observed after the 24 h GLA exposure. Following removal of the E. coli strains from the culture medium with GLA, > or = four-fold increases in MICs and/or MBCs of various antimicrobials, were observed in 42.9% and 60% of strains after exposure to 50 and 300 mg/L GLA respectively; most of these increases involved aminoglycosides. The reproducibility of GLA inhibitory effects and increase in MICs and/or MBCs for E. coli in the two different experimental procedures used, was 82% and 73% respectively. Further studies are necessary to clarify the mechanism of GLA action on E. coli and assess the clinical relevance of these findings.