The pharmacokinetic properties and local tolerance of three oxytetracycline formulations, one conventional (Engemycine, 10%) and two long‐acting (Oxyter LA, 20% and Terramycin LA, 20%) were compared in clinically healthy cross‐bred pigs following intramuscular injection of single doses (20 mg/kg body weight) in the neck region. Non‐compartmental methods were used to calculate the pharmacokinetic parameters. Assessment of local tolerance was based on serum creatine phosphokinase (CPK) concentration and a combination of echographical, macroscopic and histological examinations of the intramuscular injection site. Statistically significant differences (one‐way analysis of variance,F‐test) were obtained between the three formulations in peak plasma concentration, peak time and mean residence time. Area under the curve did not differ significantly between the formulations. Using the Studentst‐test for paired data, the two long‐acting formulations differed significantly in peak plasma concentration and peak time. Both of the long‐acting formulations differed significantly from the conventional formulation in the peak time and mean residence time. All three formulations produced an increase in serum CPK concentrations. The increase in CPK concentration was present from 6 to 24 h post treatment for Terramycin LA, from 6 to 72 h for Oxyter LA and from 6 to 96 h for Engemycine (the conventional formulation). Echographical examination of the injection site showed lesions of an inflammatory type up to 96 h after IM injection of the drug products, whereas from 7 days the lesions represented primarily scar formation. Histological examination of tissue from the injection site did not correlate with echographical scores. The results obtained in this study show that the long‐acting formulations provide significantly longer mean residence times of oxytetracycline than the conventional formulation, and that local tolerance at the IM injection site was similar for all three formulations under the experimental conditions used in this study. It can be concluded that the longacting formulations provide the advantage of a longer dosage interval when administered to pigs by intramuscular injection in the neck region at a dose of 20