Beta,beta'-Iminodipropionitrile (IDPN), a neurotoxic compound known to induce swellings in the proximal internodes of sensory and motor axons in several parts of the central nervous system (CNS), was also found to cause hydrocephalus in rats and guinea pigs. In both species, ventricular dilatation was observed within 1 week following a single i.p. injection of IDPN. While in rats the severity of hydrocephalus correlated with dose and duration of IDPN exposure, in guinea pigs studies with high doses yielded inconclusive results, and no significant temporal correlation was noted. Parallel investigations with another neurotoxic agent, acrylamide, in rats, and with IDPN in cats failed to demonstrate any change in size and shape of the cerebrospinal fluid (CSF) pathways. No signs of spontaneously occurring hydrocephalus were found in control animals. In both rats and guinea pigs intoxicated with IDPN, macroscopic and microscopic findings were consistent with the diagnosis of communicating hydrocephalus. Treatment of hydrocephalic rats with acetazolamide (500 mg/kg) markedly attenuated ventricular distention, suggesting that an overproduction of CSF by the choroid plexus is responsible for the communicating hydrocephalus following IDPN intoxication.