Abstract Bipolar bridging of cellular membrane receptors and epitopes by alloantibodies (Fab bridging the MHC antigens and Fc the Fc receptors) has been shown on a murine mast cell model to be a way of cell signaling and activation. In order to test a possible general significance of this phenomenon, another model was studied, namely guinea pig neutrophils. It was found: (1) that neutrophils from S2, S13 and BIO-AD strains both express class I (B) and class II (Ia) antigens on their surface, as detected by a Prot.A-SRBC rosetting method, after cell incubation with related alloantibodies; (2) that Fc receptors for IgG (FcγR) were specific for IgG 2 subclass, as determined by the same rosetting method after binding of preformed immune complexes (IgG 1, IgG 2 and F(ab′) 2 anti-DNP-DNP 25 BSA); and (3) that specific alloantibodies of IgG 2 subclass were able to specifically activate the neutrophil oxidative metabolism as shown by superoxide anion (O 2 −) release, detected by the luminol-dependent chemiluminescence method. Neither the IgG 1 nor F(ab′) 2 portion were able to trigger O 2 − release. This demonstrates a second situation of a cell membrane activation through alloantibody bipolar bridging.