BACKGROUND Local anesthetics inhibit mediator and free radical release from polymorphonuclear granulocytes and migration to their site of action. In a recent study, lidocaine significantly improved the alveolar-arterial oxygen difference gradients (A-aDO2) after tracheal instillation of acid in rabbits. The purpose of the current study was to evaluate the effects of lidocaine and pulse-dose steroids on human breast milk (HBM)-induced lung injury in rabbits. METHODS After Animal Care Committee approval, six adult rabbits were assigned to each of three treatments: control, lidocaine, and steroids. After induction of anesthesia and controlled ventilation, acidified HBM at pH 1.8 and volume 1.2 ml.kg(-1) was instilled into the trachea. Rabbits in the lidocaine group received lidocaine 2 mg.kg(-1) i.v. before tracheal instillation and then 2 mg.kg(-1).h(-1) i.v. continuously. Rabbits in the steroid group received 30 mg.kg(-1) methylprednisolone before tracheal instillation. A-aDO2, static compliance and blood for white cell count, and cytokine interleukin-8 (IL-8) concentration were obtained at baseline and at 1 and 4 h postinstillation. After 4 h, the rabbits were killed. The left upper lobe was isolated and excised to determine the wet/dry ratio. The right lung was lavaged with 30 ml normal saline to determine the white cell count and the concentrations of albumin and IL-8. Data were analyzed using one- or two-way anova with repeated measures and an Student-Newman-Keuls (SNK) posthoc test (P < 0.05). RESULTS All rabbits completed the protocol. A-aDO2 and CO2 tensions increased significantly at 1 and 4 h compared with baseline, although there were no differences among the treatments (P < 0.05). Compliance in the control group decreased compared with lidocaine and steroids. CONCLUSIONS We conclude that preemptive lidocaine and steroids attenuate in part HBM-induced lung injury in rabbits.