Hydergine, 12 mg per day for two weeks, has some direct activity on a variety of tasks of mental and cognitive performance. These results add support to biochemical findings that implicate the ergot alkaloids (particularly co-dergo-crine, Hydergine) in cellular activity likely to increase cortical arousal and awareness. The high dose of Hydergine used in this volunteer study was exceptionally well tolerated and did produce significant results on individual measures of central nervous system activity which might suggest the use of similar doses in patient populations. The findings of a hangover of activity after drug withdrawal and the fact that some CNS activity (serial subtraction of 17s) is not obvious until two weeks of medication would suggest the need for pharmacokinetic measures to be taken in conjunction with psychologic assessments. It would seem that a two-week schedule of repeated doses is the minimum required to produce an effect on CNS activity, but even with such a dose regimen it appears that the drug continues to exert some effect after its withdrawal.