The persistence of chloramphenicol, cephacetrile, and clindamycin in the udders of dry cows was studied after drying‐off therapy with salts of these antibiotics suspended in conventional oil bases. Antibiotic activity was not found in dry udder secretions collected 3–5 days after treatment. After equivalent doses of encapsulated formulations of chloramphenicol were suspended in the same oil bases and infused at drying‐off, most of the drug remained bound within the microcapsules; chloramphenicol concentrations higher than 10 μg/ml secretion were maintained for 3–4 weeks, but upon release from the microcapsule, the free drug was very quickly absorbed from the udder. Microcapsulated formulations of cephacetrile and clindamycin were infused at drying‐off, suspended in the same type of oil base and at similar doses to the non‐capsulated preparations. The concentrations of free drug in the secretions remained constant over a period of 2–3 weeks, although total drug (bound and free) concentrations in the udder, which were much higher than free drug levels, were progressively and markedly reduced. It appeared that after infusion of the microcapsulated preparations of cephacetrile and clindamycin, rates of drug release from the depot were equal to the rates of absorption of free drug