The mycotoxin ochratoxin A (OTA) is a chlorinated dihydroisocoumarin derivative connected through an amide-bond to L-phenylalanine. In a previous study we could show that competition with Lphenylalanine-dependent processes does not play a role in OTA neurotoxicity. To test whether the isocoumarin part is responsible for the neurotoxic effects, we determined in the present study the effects of the hydrolysis product of OTA, ochratoxin-alpha (OTa), and of ochracin on embryonic chick brain cell cultures. In addition, we investigated the interaction between OTA and ochracin regarding the neurotoxic effects. We report here that OTa did not affect brain cell cultures at concentrations up to 15 mM. With the exception of a small (20%) but signi®cant reduction in cell culture, cellular protein at concentrations above 0.3 mM, in our cell cultures' cell function, as de®ned by neutral red uptake and MTT-dehydrogenase activity, was only reduced by high OTa concentrations (1 mM). Addition of 0.1 mM OTA increased ochracin cytotoxicity as de®ned by latter parameters. No effects on cell culture NF68kD content could be detected. The results are discussed with regard to the existence of an OTA target interaction binding site. Copyright