Insulin-like growth factor-I (IGF-I) and alpha 2-macroglobulin (alpha 2-M) are believed to be involved in the development of germ cells. IGF-I is mainly controlled by concentrations of human growth hormone (HGH), influences cell proliferation and differentiation and its action is mediated by insulin-like growth factor-binding proteins (IGFBP), placental protein 14 (PP14) and prostate-specific antigen (PSA). alpha 2-M acts as a broad spectrum proteinase inhibitor and a binding protein for many cytokines and hormones, e.g. inhibin and activin. This study was designed to identify concentrations of these molecules in seminal plasma in normal semen samples of healthy men, correlations with semen quality, the relationship of IGF-I and alpha 2-M with factors affecting male fertility, and whether vasectomy influences the concentrations of these molecules. Concentrations of IGF-I and alpha 2-M in human seminal plasma were related to semen quality, basal concentrations of HGH, testosterone, IGFBP-3, soluble fibronectin receptor (sFNR), PSA and PP14 in seminal plasma and to serum concentrations of luteinizing hormone (LH) and follicle stimulating hormone (FSH). Commercially available assays were used to analyse 69 semen samples of various quality and 11 post-vasectomy samples. IGF-I concentrations in seminal plasma were significantly correlated with the percentage of morphologically normal spermatozoa (r = 0.748, P = 0.00001) and sperm concentration (r = 0.301, P = 0.011), but negatively correlated with serum FSH (r = -0.506, P = 0.00006) and PSA in seminal plasma (r = -0.388, P = 0.00009). Total alpha 2-M was significantly correlated with sperm count (r = 0.423, P = 0.0005), percentage of progressively motile spermatozoa (r = 0.444, P = 0.00019), quality of motility (sperm motile efficiency, r = 802, P = 0.00001) and straight line velocity (r = 0.411, P = 0.0013). Correlation between the sperm concentration and HGH in seminal plasma was weak (r = 0.287, P = 0.015). Vasectomy reduced the concentration of total alpha 2-M (P = 0.00008) and HGH (P = 0.0068) in the seminal plasma; IGF-I was also reduced after vasectomy when the total ejaculate amount was considered. Thus IGF-I and alpha 2-M are significant for the germ cell development: IGF-I in the maturation of spermatozoa and alpha 2-M in progressive motility.