The effects of phenoxymethylpenicillin on the bacterial flora of the vagina were investigated in 6 women who fulfilled the criteria of 'normality': predominance of lactobacilli, and absence of Enterobacteriaceae and fungi. Fourteen healthy women were enrolled and followed longitudinally; 8 of these were subsequently excluded because of divergence from normality. Following penicillin treatment, Gram-negative rods appeared in 4 of the remaining 6 women, and in 1 subject heavy growth of Candida albicans resulted. In 5 of the women there was no change in the lactobacillus count and a rise in pH was found in 4 subjects. In 1 woman, lactobacilli disappeared completely and were replaced by Escherichia coli. Concomitantly, high concentrations of endotoxins were found in the vaginal fluid. Treatment with penicillin may interfere with the normal vaginal bacterial flora and provide an environment favorable for Enterobacteriaceae and fungi.