A total pollutant load control system (TPLCS) was implemented in the Seto Inland Sea in 1979 to reduce the water pollution and the frequency of red tides. We estimated primary production from 1981 to 2010 to determine the effects of reducing the nutrient loadings from the surrounding land. While primary production has decreased overall in the Seto Inland Sea in response to the TPLCS and the associated reductions in the total nitrogen (T-N) and phosphorus (T-P) loads from land since 1981, the reductions were limited to 4 of its 11 subareas. Primary production has increased in the Harima Nada but has been stable in the Bingo Nada subarea, reflecting the fact that the T-N and T-P stocks have not decreased in these subareas over the study years. The inconsistent responses of the 11 subareas suggest that the characteristics of each subarea should be considered when environmental management measures are established and implemented in the Seto Inland Sea. The controls on the nutrient loadings according to the TPLCS should be modified to permit better management of this semi-enclosed sea.