The receptor for the inflammatory peptide C3a has scarcely been examined on human cells. This work demonstrates that human tumor‐derived basophilic granulocytes express C3a receptors, and presents parts of the hitherto unknown C3a‐signal transduction. When incubated with IL‐3, these cells specifically liberated histamine on C3a stimulation. Independent from IL‐3, 240000 ± 100000 receptors per cell with a Kd of 5.6 ± 0.9 nM were determined. (Ca2+)j increased from 120 ± 35 nM to 300 ± 80 nM after a C3a challenge, as measured by digital imaging fluorescence microscopy, and rested at its basal level in the presence of C3a‐desArg, the immediate catabolic product of C3a in vivo. This (Ca2+ )i increase could be completely desensitized homologously by C3a as well as inhibited by up to 75% by pertussis toxin. Thus, tumor‐derived basophils are suitable for cloning of the human C3a receptor.