Leukocytes from mite sensitive asthmatic patient were challenged with the allergen and the supernatant was assayed for histamine and immunoreactive-leukotriene C4 (i-LTC4). The release of histamine was quantitated by an automated fluorometric technique and i-LTC4 was determined using a commercial radioimmunoassay kit. The results of analysis of the supernatant by high speed liquid chromatography, together with observations of modulation of the formation by agents, indicated that i-LTC4 consisted of LTC4 with a little amount of LTD4. i-LTC4 was generated as a result of basophil activation but not derived from the other cells such as monocytes and eosinophils. Allergen induced a concentration-dependent release of histamine and i-LTC4 and the maximal release of histamine and i-LTC4 occurred at the same dose of the allergen. At optimal concentration of the allergen, basophils produced 20.4 +/- 17.9 ng of i-LTC4/10(6)-cells (mean +/- S.D., n = 39) and histamine release was 55.6 +/- 20.1% of total histamine. There was a significant correlation in the capacity of leukocytes to release histamine and i-LTC4 (r = 0.47, p less than 0.01). We found a correlation between maximal histamine release or cell sensitivity, allergen concentration for 50% histamine release, and a ratio of specific IgE to mite to total IgE in the serum, but the amount of i-LTC4 failed to correlate significantly with the ratio. The releasability and the cell sensitivity of asthmatic patients' cells to the allergen for histamine release paralleled the severity to symptoms, but this correlation was not significant in i-LTC4 generation.