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To study effects of cigarette smoke on the cytoplasmic motility (CM) of alveolar macrophages (AM), we measured remanent field strength (RFS) in guinea pigs with and without systemic capsaicin pretreatment in vivo. Four days after instillation of 3 mg/kg ferrimagnetic particles (Fe3O4) into the trachea, RFS was measured at the body surface immediately after magnetization of the Fe3O4 particles by an externally applied magnetic field. RFS decreased with time because of particle rotation (relaxation), which is thought to be correlated to CM of AM. The initial relaxation curve was fitted to an exponential function. The relaxation rate (lambda 0) increased during cigarette smoke inhalation and returned to baseline values within 5 min, and with the inhalation of the smoke of as many as three cigarettes, peak lambda 0 increased in animals without capsaicin pretreatment. However, cigarette smoke decreased lambda 0 with an increased number of cigarettes in animals with capsaicin pretreatment. Injection of nicotine or acetylcholine increased respiratory resistance to a degree similar to that observed with cigarette smoke, but it did not change lambda 0. However, substance P (SP) increased lambda 0, and repeated administration of SP produced a significant tachyphylaxis in animals with and without capsaicin pretreatment in a fashion similar to that noted with cigarette smoke inhalation. Acrolein decreased lambda 0 in animals with and without capsaicin. Colchicine inhibited the cigarette smoke-induced increase in lambda 0.(ABSTRACT TRUNCATED AT 250 WORDS)