The kinetics of blood-brain barrier (BBB) choline transport in streptozocin-induced diabetic rats were compared with those of age-matched vehicle-injected control rats. The brain uptake index (BUI) of choline in diabetic rats (13.9 +/- 1.1%) was significantly lower than that in control rats (22.6 +/- 0.7%) (P less than .05). This alteration in brain choline uptake appeared to occur in long-standing (9 wk) diabetes. Thus, acute hyperglycemia and diabetes mellitus for shorter periods (3 wk) did not significantly alter the BUI of choline. Insulin (8 U/kg) treatment for 5 days did not alter BUI in diabetic rats (12.9 +/- 0.9%). The maximal velocity of BBB choline transport (Vmax) in diabetic rats (0.14 +/- 0.07 nmol . min-1 . g-1) was significantly lower than the Vmax in control rats (2.2 +/- 0.8 nmol . min-1 . g-1) (P less than .05). The Km of choline transport in diabetic rats (120 +/- 70 microM) was modestly but not significantly lower than that in control animals (400 +/- 160 microM). Similarly, the constant of the nonsaturable component of the transport (Kd) in diabetic animals (0.5 +/- 0.07 microliter . min-1 . g-1) was not significantly different from that in control rats (0.9 +/- 0.3 microliter . min-1 . g-1). The data indicate that diabetes mellitus in rats is associated with a decreased BBB choline transport.