Abstract1. The effects of single doses of dimethindene (retard) 2·5 mg, chlorpheniramine (TD) 12mg and placebo on a battery of physiological, performance and subjective measures were studied in a double‐blind, crossover study in 12 healthy subjects.2. Dimethindene had a different EEG profile from chlorpheniramine; while both active drug treatments were associated with an increase in 8·0–13·0 Hz waveband activity, dimethindene alone produced less 2·0–4·0 Hz activity.3. The two active drugs were associated with an improvement in tapping rate. Dimethindene had no effect on simple reaction time, while chlorpheniramine was associated with a slowing in this measure.4. Subjective measures generally indicated an improvement in general alertness and contentedness with both dimethindene and chlorpheniramine.5. It is concluded that single doses of sustained‐release formulations of these antihistamines are slightly stimulant in effect and are useful where sedation in