The effects of iv succinylcholine (SCh) on cerebral blood flow (CBF), muscle afferent activity (MAA), electromyographic activity (EMG), visible fasciculations, and Pa(CO2) were tested in 12 dogs anesthetized with 0.87% end-expired halothane (1 MAC). Six dogs (group I) received treatments of both SCh 1.0 mg/kg iv and saline placebo 3.0 ml iv. Fasciculations and substantial increases in EMG activity were observed in all six dogs given SCh. At the onset of fasciculations, there were parallel increases in MAA and CBF to peak values of 466% ± 77% of control (mean ± SE) and 136% ± 5% of control, respectively, at the 1-min measurement point. Thereafter, both MAA and CBF declined toward control values. An additional six dogs (group II) were prepared as above; however, they were pretreated with a defasciculating dose of pancuronium 0.01 mg/kg iv 5 min before being given SCh 1.0 mg/kg. These dogs were also given treatments of saline placebo 3.0 ml iv during another portion of the study. None of these six dogs had visible fasciculations following SCh, and only in one was slight EMG activity detected. Following iv SCh, there were parallel increases in both MAA and CBF. The peak MAA value of 255% ± 56% of control occurred at the 1-min measurement point and was followed by a gradual decline in MAA. CBF increases were greatest during the periods of greatest MAA (i.e., the 1- to 3-min measurement points). The largest increase in CBF (128% ± 9% of control) occurred at the 3-min measurement point. Following SCh in both groups I and II, there were significant increases in Pa(CO2), but these increases could not account for peak CBF values in either group. The authors conclude that CBF increases following iv SCh are primarily related to SCh-induced increases in MAA and secondarily related to SCh-induced increases in Pa(CO2). These data demonstrate that it is not the presence or absence of fasciculations per se that determines the cerebral response to SCh; instead, it is the effect of SCh on the muscle afferents that correlates with the peak cerebral response.