In Balb/C mice, painting the skin with ovalbumin (OVA) over a period of 14 days resulted in sensitization of the animals. This was documented by the appearance of OVA-specific IgE and IgG1 antibodies and increased total serum IgE levels. In addition, in regional (inguinal) lymph nodes of sensitized animals, OVA-specific T cell proliferative responses and increased IgE and IgG production could be detected in vitro. Sensitized animals also developed immediate cutaneous responses to intradermal injection of OVA. In contrast to previous results following OVA sensitization via the airways, increased airways responsiveness to electrical field stimulation (AREFS) of tracheal smooth muscle preparations was not observed in skin-sensitized mice. Only 24 h after a single local challenge of the airways with aerosolized OVA on Day 14 could a significant increase in AREFS be observed in skin-sensitized but not nonsensitized control mice. These data indicate that sensitization of Balb/C mice to OVA via the skin provides an effective means for inducing a systemic IgE and IgG1 antibody response and immediate cutaneous hypersensitivity. Despite these IgE and IgG1-mediated responses, however, the development of altered function as reflected in an increase in AREFS was dependent on challenge with the allergen via the airways.