Twelve adult Collie dogs were studied to determine the effects of ivermectin on neurotransmitter metabolites released from the brain into the cerebrospinal fluid (CSF) and on CSF pressure. Ten of the 12 Collies were given ivermectin orally at a concentration of 200 micrograms/kg body weight. Three of these 10 Collies showed clinical signs of ivermectin-induced toxicosis which progressed into a state of unresponsive recumbency in 2 dogs. Cerebrospinal fluid pressures and neurotransmitter metabolite concentrations in cisterna magna CSF were analysed 49 to 50 hours after administration of ivermectin in 6 of the 10 treated dogs, and in the 2 untreated control Collies. Cerebrospinal fluid pressures were within normal limits in all dogs. However, compared to the CSF concentrations in the 2 untreated and 3 non-reactive Collies, the 2 ivermectin-reactive Collies still in recumbency had elevated CSF concentrations of homovanillic acid (HVA), a metabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin. These findings suggest an association between altered neurotransmission and severe ivermectin-induced neurological abnormalities. No evidence of elevated intracranial pressure was found.