The insulin or proinsulin response of the isolated rat adipocyte was destroyed by preincubation with trypsin. After 120 minutes, biological responsiveness partially regenerated. Similarly, the biological responsiveness of the isolated fat cell to non-suppressible insulin-like activity (NSILA) was only partially destroyed following trypsin digestion, and did not regenerate. In contrast to the above, cyclic AMP or dibutyryl cyclic AMP effects were unaltered by trypsin or neuraminidase digestion. Concanavalin A, a plant lectin, was shown to stimulate glucose utilization in the isolated fat cell with a dose-response curve qualitatively similar to insulin. Neuraminidase digestion of the isolated fat cell destroyed its biological responsiveness to both Concanavalin A and insulin. Methyl α-D-glucopyranoside, a known Concanavalin A inhibitor, blocked both Concanavalin A and insulin stimulation of glucose utilization and inhibition of lipolysis in the isolated fat cell. When fluorescein labelled Concanavalin A was utilized, surface staining was seen on the isolated fat cell. This staining was markedly reduced after treatment with methyl--alpha;-D-glucopyranoside or prior incubation with insulin. It would appear that Concanavalin A shares many of the biological properties of insulin, and that binding mechanisms for both in the isolated fat cell are similar. However, in contrast to polypeptide hormones or Concanavalin A, cyclic AMP or dibutyryl cyclic AMP exert their biological effects apparently independent of surface receptors mechanisms. 1 This research was conducted under VA Research Project # 2 , 3499-01, -02; 8036-01, -03 and supported in part by U.S.P.H.S. Grants AM-15509, AM-18022.