Recent reports indicate that children receiving a fifth consecutive dose of DTPa vaccine have a moderate likelihood of developing a large injection site reaction, the etiology of which remains unknown. We assessed the frequency, severity and outcome of local reactions in 205 children who had participated in earlier studies of DTPa-based vaccines and were due for a fifth dose at 4-6 years. DTPa.IPV vaccine was given intramuscularly in the deltoid. To explore the role of cell-mediated immunity in local reactions we applied epicutaneous (patch) tests at the same visit, using code-labeled solutions of DTPa.IPV, DT, Pa, IPV, alum solution and saline, leaving them in place for 48 h. Subjects were assessed by research staff on the following day. Injection site redness or swelling >/=50 mm diameter was present in 24.4 and 20.5%, respectively, but none of the subjects had fever or persistent limitation of arm movement. Large local reactions were more common in bigger children (P<0.01) but not in those with allergy/atopy. Large reactions resolved within 14 days. Positive skin tests (erythema) occurred at 85 test sites in 51 of 187 evaluable children, principally with DTPa.IPV, IPV and alum solutions. However, only DT and Pa solutions caused positive tests significantly more often in children with injection site redness > or =50 mm than in non-reactors (P < 0.05, odds ratios 5.2 and 6.1, respectively). Presence of alum in most test solutions might have confounded the results as it caused non-specific inflammation when applied alone. We conclude that local reactions to a fifth dose of DTPa-type vaccine are frequent and sometimes extensive but not incapacitating and that concurrent skin testing has potential to identify the vaccine antigens and immune mechanism contributing to local reactions with more refinement of the method.