Maternal smoking is a major risk factor for sudden infant death syndrome. Protein kinase C (PKC) and neuronal nitric oxide synthase (NOS) activities within the dorsocaudal brainstem (DB) mediate critical components of respiratory drive and could be implicated in SIDS. Thus, exposure to smoking during fetal life could modify the expression of these kinases in the DB. Rats were exposed to cigarette smoke or room air (Sham) from day 2 to 22 of pregnancy. Immunoblots of DB lysates at 2 days postnatally revealed no differences in PKC-alpha, PKC-beta, and endothelial NOS expression. However, PKC-gamma, PKC-delta, and neuronal NOS immunoreactivities were reduced in the cigarette smoke group. We conclude that gestational smoking is associated with selective reductions in PKC and NOS isoforms within the DB, which could decrease respiratory drive and lead to enhanced hypoxic vulnerability in infants of smoking mothers.