So far, a little is known about transition from normal to focal epileptic brain, although disruption in blood-brain barrier and albumin had recently involved. The main objective of this work is to characterize the response of cultured human astrocytes to plasma albumin, including induction of DNA synthesis. Cortical tissue was obtained from 9 patients operated from temporal lobe epilepsy. Astrocytes were cultured for 3-4 weeks and cytosolic calcium concentration ([Ca(2+)]c) was measured. Bovine and human plasma albumin were used. We observed that low albumin concentration decreases [Ca(2+)]c, while higher concentration, induces increase in [Ca(2+)]c. It was shown that increase in [Ca(2+)] c was mediated by inositol 1,4,5-trisphosphate and released from internal stores. Increase in [Ca(2+)]c was reduced to 19% by blocking the transforming growth factor-beta (TGF-βR) receptor. Albumin induces DNA synthesis in a dose-response manner. Finally, induction of DNA synthesis can be partially blocked by heparin and block of TGF-β; however, the combination of both incompletely inhibits DNA synthesis. Therefore, results suggest that mechanisms other than Ca(2+) signals and TGF-β receptor activation might induce DNA synthesis in a lesser degree. These results may be important to further understand the mechanisms involved in the transition from normal to focal epileptic brain.