Inhalation of the dust of industrial hard metal (IHM), which consists of tungsten carbide, Co and other metals, causes asthma and interstitial fibrosis in workers. Dissolution of the metals may occur in. the lungs. Intratracheal instillation of guinea pigs with IHM causes up-regulation of NO pathways and hyporeactivity to inhaled methacholine (MCh). To determine if neural regulation of airway diameter is also affected by IHM, we examined the effects of C02+, Cd2+ and Ni2+ on electrical field stimulation-induced neurogenic contractile and relaxant responses of guinea-pig tracheal strips. The effects of the metals (10^-6 M; 30 min) were examined in strips at resting force or contracted with MCh (3 x 10^-1 M), either in the absence or presence of indomethacin (In. 10^-6 M). No metal had any effect on the eNANC contraction phase or relaxation responses under any condition, or affected contractions or relaxations obtained in the absence of In. CO2+ inhibited contractions in MChcontracted strips (+In). Cd2+ and Ni2+ potentiated slightly contractions obtained in MCh-contracted strips (+In), but inhibited contractions obtained in the absence of MCh (+In). We conclude that following dissolution in the airway wall, metals contained in IHM may alter cholinergic neurogenic pathways.