Objective  To identify possible synergistic associations of hookworm and other helminths. Method  Cross-sectional survey of all households within 10 km2 of Americaninhas, a rural community in Minas Gerais, Brazil. We determined the prevalence and intensity of single and multiple helminth species infection in an age-stratified sample of 1332 individuals from 335 households. Results  Hookworm was the most prevalent helminth infection (68.2%), followed by Ascaris lumbricoides (48.8%) and Schistosoma mansoni (45.3%). Overall, 60.6% of individuals harboured mixed helminth infections. Multivariate analysis indicated significant positive associations for co-infection with hookworm and S. mansoni and for co-infection with hookworm and A. lumbricoides. Co-infections with hookworm and A. lumbricoides resulted in higher egg counts for both, suggesting a synergistic relationship between these species, although, we found important age differences in this relationship. However, the intensity of S. mansoni or A. lumbricoides co-infection did not differ from that of mono-infection. Conclusion  These results have implications for the epidemiology, immunology and control of multiple helminth infections. More research is needed to examine the rates of re-infection and immune responses after chemotherapy, and to what extent the effects of polyparasitism are altered by chemotherapy.