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Problem Natural killer (NK) cells are regulated through NK cell receptors such as killer cell immunoglobulin-like receptors (KIRs). KIRs are suspected of being involved in the causes of recurrent miscarriage (RM) as a higher proportion of activated NK cells were observed in women with RM when compared with that in controls. The aim of this study was to investigate if KIR genes coding for receptors known to have as ligands HLA class I molecules are correlated with RM. Method of study  A matched case–control study was carried out in 68 south Brazilian Caucasian patient couples with RM and 68 control fertile couples. KIR genes were typed by PCR-Reverse SSO method. Results The rate of possession of an elevated number of activating KIR genes (positive for five or six activating KIR genes out of six different activating KIR genes analyzed) in RM patient women was significantly higher ( P = 0.0201) when compared with that in control fertile women. These data suggest that women carrying a high content of activating KIR genes have about threefold increased probability to develop RM [OR = 2.71; 95% CI (1.23–6.01)]. Conclusion  Our results indicate that RM could be associated with NK cell activation mediated by a profile rich in activating KIR genes. [ABSTRACT FROM AUTHOR]