Abstract Rationale Cow's milk hypersensitivity (CMH) is one of the most common food allergies in children. We investigated if the development of tolerance to cow's milk (CM) by the age of four can be predicted with a prick skin test (PST), and measurements of total or specific IgE in the serum, taken at the time of diagnosis of CMH. Methods Infants with immediate (n=95) or delayed (n=67) reactions to CM, which were confirmed by a double-blind placebo-controlled food challenge before the age of 1 year were prospectively followed to the age of 4. The PST (duplicate tests) with a CM based formula and the measurement of milk-specific IgE by CAP FEIA were carried out at the same time that the initial milk challenge was performed. CMH status was assessed annually by CM challenges. Results By the ages of 2, 3 and 4, children with delayed reactions developed tolerance to CM faster than those with an immediate reaction: 64%, 92% and 96% vs. 31%, 53% and 63% respectively. A wheal size of Conclusions PST and milk-specific IgE in the serum are useful prognostic indicators of the development of tolerance to CM in infants with CMH.