BACKGROUND: Endothelial cells cultured in vitro are commonly used as a model for testing the effects of therapeutic or detrimental agents on endothelium. Cells originating from different vascular beds display, however, a heterogeneity of function and phenotype. Here we compared the production of angiogenic growth factors and the sensitivity to exogenous growth factor stimulation of two popular endothelial cell types. METHODS: Experiments were performed on human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1) incubated in optimal conditions for 24–48 h. RESULTS: The profile of the spontaneously produced growth factors differed significantly between the two different cell lines tested. HUVEC did not produce detectable amounts of VEGF, whereas HMEC-1 released 24.9 pg/ml and this amount was significantly increased in response to IL-1β. Instead, HUVEC produced high concentrations of soluble form of VEGF receptor-1 (VEGF-R1), whereas the release of VEGF-R1 from HMEC-1 was 10-fold lower. Small amounts of bFGF were found in media from both cell types, but higher levels were detected in HMEC-1 cultures. In contrast, the secretion of interleukin-8 (IL-8) and matrix metalloproteinase-1 (MMP-1) were 30- to 40-fold higher in HUVEC than in HMEC-1. The cell types differed also in their sensitivity to exogenous growth factors. The basal proliferation of HUVEC was very low but could be effectively stimulated by supplementation with VEGF or bFGF. HMEC-1 proliferated spontaneously and their proliferation rate was not further augmented by growth factors. Similarly, the spontaneous outgrowth of capillaries was negligible in HUVEC but well pronounced in HMEC-1. CONCLUSIONS: Production of angiogenic agents and sensitivity to exogenous growth factors is cell-type dependent. HUVEC, which do not release VEGF, can be easily stimulated with exogenous factors, whereas HMEC-1, which are able to produce VEGF, do not respond well to the additional stimulation. Our study demonstrates that conclusions resulting from in vitro experiments performed on only one type of endothelial cells can be misleading.