Prolactin (PRL) is a 23-kDa protein hormone that is synthesized mainly by the anterior pituitary gland. However, PRL can also be synthesized and secreted by extrapituitary tissues, particularly immune cells. A biallelic polymorphism (-1149 G/T) in the prolactin promoter has been shown to be functionally important, as modulation of prolactin expression has been associated with SLE in some populations. We have performed an association study using Mexican patients with SLE. We used qPCR to determine the SNP allele and genotype frequencies. We did not find statistically significant differences in allele and genotype frequencies between patients and healthy controls. However, we found a statistically significant association between the G allele and the presence of anti-dsDNA antibodies in serum (Allele frequency (G): P = 0.005; Genotyping frequency (GG): P = 0.001, OR = 7.8, 95% CI 3.59-27.1). Our data demonstrate that the prolactin promoter polymorphism -1149 G/T does not significantly contribute to SLE disease susceptibility but does predispose carriers to other immunological changes.