THE PHYSIOLOGICAL AND anatomical aberrations that result in hemorrhage from cerebral arteriovenous malformations (AVMs) remain unclear. In an attempt to clarify which conditions may predispose to hemorrhage, we examined clinical and physiological indices on presentation groups of either hemorrhage or nonhemorrhage in a large cohort of patients (n = 449). Variables examined included AVM size, type of venous drainage, transcranial Doppler (TCD) velocities, feeding mean arterial pressure (FMAP), and draining vein pressure. TCD and pressure data were obtained before any treatment. Age (mean ± standard deviation) at the time of presentation was 33 ± 13 years and did not differ between groups. Patients with small (≤ 2.5 cm) AVMs presented more frequently with hemorrhage (90%) than did patients with medium (> 2.5 and ≤ 5.0 cm; 52%) or large (> 5.0 cm; 50%) AVMs (P= 0.0001). The 48 of 94 AVMs (51%) with deep venous drainage were more likely to have hemorrhage (P= 0.0219) than were those with superficial drainage (24 of 73 [33%]). Deep drainage was a predictor of hemorrhage even in the subgroup of medium and large supratentorial AVMs (P= 0.005). There was no difference in draining vein pressure (n = 18) between groups (21 ± 10 and 19 ± 11 mm Hg, respectively;P= 0.7812). FMAP (n = 52) was higher in the hemorrhage than in the nonhemorrhage group (44 ± 13 versus 34 ± 10 mm Hg;P= 0.0007) but was only weakly related to the size of the lesion (largest dimension) (y= -0.74x + 40;r= 0.09). Unlike FMAP, TCD velocities correlated well with largest dimension (n = 76;y= 15x+ 86;r= 0.55). Although the hemorrhage group demonstrated lower mean flow velocities (94 ± 40 versus 114 ± 33;P= 0.0236), the absolute differences were small, suggesting that TCD indices are more related to size than propensity for hemorrhage. By the use of a multiple logistic regression model, in the subset of patients with medium or large AVMs and superficial venous drainage (the group with the lowest identified risk of intracerebral hemorrhage), FMAP had a strong influence on the incidence of intracerebral hemorrhage, (P= 0.0086), but TCD velocities did not. In summary, smaller nidus size and the presence of deep venous drainage are independent predictive factors that may increase the risk of hemorrhage from AVMs. Finally, higher FMAP is an important factor in the pathophysiology of hemorrhage from AVMs and not just a consequence of lesion size.