Low doses of environmental allergens have been proposed to increase bronchial hyperreactivity in sensitised individuals, without causing immediate asthmatic reactions. The primary aim of the present study was to evaluate whether repeated low doses of allergen, that do not cause overt bronchoconstriction, cause augmented non-specific bronchial reactivity. A secondary aim was to evaluate whether any changes in reactivity are associated with increased variability of lung function, and whether signs of inflammatory activity could be found. To do this, mild asthmatic patients without regular symptoms, but with both immediate and late reactions in response to a high dose of inhaled cat allergen extract, were included in a double blind, placebo controlled, cross-over study in which a low dose of allergen was administered on four consecutive days (Monday to Thursday). The dose of allergen was individualised for each patient, and was calculated to be 25% of the total dose given to produce an immediate and late response at screening. Repeated low dose allergen exposure produced a significant increase in methacholine reactivity compared to placebo, whereas FEV1 in the morning did not significantly change during the allergen week. Each low dose allergen exposure caused small changes in FEV1 (approximately 7% drop), which was significant vs. placebo only on day 2 (Tuesday). During the allergen week, six of eight patients reported asthma symptoms on at least one occasion, and variability in lung function, measured with a portable spirometer, was increased. Repeated low doses of allergen also produced a significant increase of P-ECP vs. placebo, without a significant rise in circulating eosinophils. However, no significant changes in circulating CD3, CD4, CD8, CD19, or CD25 cells were found, evaluated by FACS analysis. We conclude that low doses of allergen produce signs of a mild exacerbation of asthma, including increased bronchial reactivity to methacholine. This clinical model may be useful to evaluate both the pathophysiological mechanisms of asthma, and the effects of novel anti-asthma drugs.