The relationship between atopy and bronchial hyperresponsiveness (BHR) on the one hand and the annual rate of decline in FEV1 and the annual exacerbation rate on the other was studied in 71 adult patients with asthma during a period of 2 yr. Atopy (based on seven RAST tests) and BHR (PC20-histamine) were assessed at the start of the 2-yr follow-up period, and they were related to the decline in FEV1 (FEV1 slope) and the exacerbation rate. The results indicated that BHR was related to the FEV1 slope independently of the FEV1 level. The mean prebronchodilator FEV1 slope was -94 ml/yr (-39 to -149 ml/yr) in patients with PC20 less than or equal to 2 mg/ml and -21 ml/yr (+34 to -76 ml/yr) in patients with PC20 greater than 2 mg/ml. Atopy alone was not related to the FEV1 slope. However, in atopic patients BHR was related to a more pronounced FEV1 slope than in nonatopic patients. The slope of the postbronchodilator FEV1 was comparable with the slope of the prebronchodilator FEV1, which may indicate that the loss of FEV1 was not only due to increased bronchospasm but also to fixed obstruction. BHR and atopy were not associated with the exacerbation rate. Asthmatic patients with atopy and marked BHR should be looked upon as patients with a risk of developing progressive airflow obstruction.