The present study was designed to determine and compare the plasma disposition and pharmacokinetics of penicillin G sodium following intravenous (i.v.) administration to horses, ponies and donkeys. The plasma disposition and pharmacokinetics of penicillin G was similar in horses, ponies and donkeys (elimination half-lives--39.0, 27.3 and 31.5 min, respectively) and a dosage interval of 6-8 h would be suitable to treat infections caused by susceptible bacteria. Although penicillin G was absorbed rapidly following nasogastric administration, the systemic availability was low (0.12-0.34%), therefore oral administration would be unsuitable for systemic antimicrobial therapy in the equine. The elimination of penicillin G into the gastrointestinal tract following i.v. administration and the absorption of penicillin G from the gastrointestinal tract following oral administration were studied in two ponies with cannulated caecal fistulas. A low concentration of penicillin G (< or = 0.6 micrograms ml-1) was measured in caecal liquor following i.v. administration, however the risk of development of antimicrobial-associated colitis would be high following oral administration of penicillin G since high concentrations of drug (4.96-157.12 micrograms ml-1) were measured in caecal liquor.