Co-occurrence of fumonisin B₁ (FB₁) and aflatoxin B₁ (AFB₁) in maize has been demonstrated in many surveys. Combined-exposure to FB₁ and AFB₁ was of concern to the Joint FAO/WHO Expert Committee on Food Additives because of the known genotoxicity of AFB₁ and the ability of FB₁ to induce regenerative proliferation in target tissues. Humans living where maize is a dietary staple are at high risk for exposure to both mycotoxins. Our work has focused on Guatemala, a country in Central America where maize is consumed in large amounts every day and where intake of FB₁ has been shown to be potentially quite high using biomarker-based studies. In 2012 a survey was conducted which analysed maize samples for FB₁ and AFB₁ from all 22 departments of Guatemala. The results show that the levels of AFB₁ exposure are also potentially quite high in Guatemala, and likely throughout Central America and Mexico. The implications of co-exposure for human health are numerous, but one area of particular concern is the potential of FB₁ to modulate AFB₁ hepatoxicity and/or hepatocarcinogenicity. Both the mechanism of action of FB₁ and its ability to promote liver carcinogenicity in rats and rainbow trout is consistent with this concern. In farm and laboratory animals FB₁ inhibits ceramide synthases, key enzymes in de novo ceramide biosynthesis. The inhibition of sphingolipid signalling pathways mediating programmed cell death and activation of pathways stimulating cell proliferation in livers of individuals exposed to AFB₁ could contribute to the tumorigenicity of AFB₁. Studies investigating the health effects of either toxin should consider the potential for co-exposure to both toxins. Also, in countries where maize-based food are prepared by alkaline treatment of the maize kernels, the effect of traditional processing on AFB₁ levels and toxicity needs to be determined, especially for maize highly contaminated with AFB₁.