Prophylactic efficacy of 100 mg of long-acting oxytetracycline (OTC) given IM to neonatal pigs within 12 hours of birth was evaluated in a swine herd. The herd had a history of increased neonatal mortality, diarrhea, foot abscess, and arthritis in nursing pigs. Two trials were conducted in which liters and individual pigs were the treatment groups of interest. In both trials, OTC treatment failed to reduce mortality, diarrhea, or arthritis or the need for subsequent antimicrobial therapy (P greater than 0.05). Preweaning weight gains were not increased (P greater than 0.05) in treated pigs. However, in the individual pig trial, foot abscess rates were significantly (P = 0.01) lower in treated pigs (3.7%) than in nontreated pigs (8%). Aerobic bacteria isolated from pigs with diarrhea, arthritis, or foot abscess had minimum inhibitory concentrations for OTC greater than or equal to 64 micrograms/ml or were classed as resistant on the basis of disk-diffusion tests.