Hypertonic and hypotonic contrast media and/or solutions were injected intracerebrally and into the subarachnoid space of rats, and the effects on the central nervous system (CNS) were investigated. Additionally, rabbits were injected intracisternally with nonionic contrast media that were either isotonic or hypertonic to the cerebrospinal fluid, and their behavior was observed. Both hypertonic and hypotonic contrast media and/or control solutions caused CNS depression, but not excitation. Even slight hypertonicity affected motor coordination. The sedating effect of nonionic contrast media, when given in the large doses customary in in vivo experiments, can mask their inherent epileptogenicity and give a false impression of a high safety margin.