To investigate systemic antimuscarinic activity after the intravesical administration of 6 mg of atropine sulphate. Ten subjects were recruited to an open study in accordance with strict inclusion and exclusion criteria. Each subject received an instillation of 6 mg atropine sulphate diluted to 20 mL with normal saline. All variables were measured at baseline (before instillation) and the instilled solution retained for at least 2 h. After instillation systemic antimuscarinic activity was monitored every 20 min for 2 h then hourly for the next 4 h. The measurements included blood pressure, sublingual temperature, pulse rate, peak expiratory flow rate, lacrimation and salivation rates; all variables were analysed statistically. Facial skin was also observed for hyperaemia. All subjects were questioned about any known symptoms produced by antimuscarinic agents. The heart rate was recorded continuously before and after instillation using a Holter monitor. None of the variables changed significantly after instillation and the Holter analysis showed no relevant variation in heart rate. All subjects consistently denied any antimuscarinic symptoms. One subject had mild cutaneous hyperaemia, as reportedly occurred consistently when her bladder was distended (> 500 mL). Immediate catheterization drained 600 mL and the hyperaemia resolved. The failure to detect systemic antimuscarinic activity at a dose which has previously been shown to suppress detrusor activity suggests that intravesical atropine therapy is safe for further study by clinical trial, and might provide a treatment for detrusor hyper-reflexia that is free from side-effects.