Two associations of antituberculous drugs were tested for their ability to prevent infection in calves orally inoculated with Mycobacterium paratuberculosis in the first few days of life. The associations were: rifampin (RMP) + clofazimine (CFA) and rifampicin (RMP) + streptomycin (SM) + pyrazinamide (PZA). Drugs were administered daily in the milk, for a period of seven months, starting the day after experimental inoculation. The RMP+SM+PZA association prevented the intestinal colonization and infection was avoided, while RMP+CFA was only able to delay M. paratuberculosis excretion in the feces, in comparison to controls.