Local reactions to glatiramer acetate are common, but few cases of hypersensitivity reaction have been reported. We present 3 patients with multiple sclerosis who suffered immediate-type local reactions after subcutaneous injection of glatiramer acetate. Skin prick test (SPT), intradermal test (IDT), and determination of immunoglobulin (Ig) E to glatiramer acetate were performed in patients and controls (enzyme-linked immunosorbent assay). The results of SPT were all negative. Those of IDT in controls were negative at concentrations below 200 microg/mL, but positive for patients 1, 2, and 3 at 2, 20, and 200 microg/mL, respectively. Serum IgE to glatiramer acetate in patient 1 was 2.1 times higher than in the controls, whereas no differences were found between controls and patients 2 and 3. Glatiramer acetate was safely reintroduced in patients 2 and 3. The results obtained for patient 1 suggest that an IgE-mediated mechanism was probably involved. In conclusion, IDT and serum IgE determination to glatiramer acetate seem useful for identifying allergic reactions among the common local reactions induced by this drug.