In primary cultures of cerebellar granule cells kainate produced marked influx of 45Ca2+, partially sensitive to the N-methyl-D-aspartate (NMDA) antagonist, 3-(+/-)-2-carboxypiperazin-4-yl)- propyl-1-phosphonic acid (CPP), indicating involvement of an NMDA receptor-sensitive component that may be secondary to kainate-induced glutamate release. Sodium removal partially inhibited kainate's effect. Quisqualate also produced influx of 45Ca2+, but with lower efficacy and higher potency than kainate. This action of quisqualate was unaffected by CPP and by sodium removal. Preincubation of cells with the plant lectin concanavalin A (Con A), but not with its succinyl derivative, enhanced quisqualate-induced calcium influx, and to a lesser extent kainate's effect. Inclusion of quisqualate in preincubation medium antagonized Con A potentiation of quisqualate response. Also Con A was ineffective when included in the incubation medium only, without preincubation. Preincubation of rat brain cortical membranes with Con A but not with succinyl Con A increased the binding of the AMPA receptor agonist, [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([3H]AMPA). The results suggest that Con A enhancement of quisqualate response possibly involves the modification of an AMPA recognition site and requires preincubation in the absence of an agonist (here quisqualate).