Drugmakers advanced, with the two leading percentage gainers in the Nikkei - Astellas Pharma jumping 3.69% and Chugai Pharmaceutical climbing 1.75%. Daiichi Sankyo rose 1.09%.
Nikkei share average lost 0.81% to 29,844.81 by 0208 GMT, after hitting the 30,000 mark for the first time in more than two weeks on Monday. The broader Topix fell 0.74% to 1,968.80
"The market fundamental is strong. But ultimately the stimulus packages in the US and the direction of the long term interest rates could determine the move of the Japanese market."
Japanese Prime Minister Yoshihide Suga will chair a coronavirus meeting later in the day and could further restrict a travel subsidy programme to contain mounting infections.
However, Toyota Motor rose 4.4% as investors welcomed the revamp of its Mirai hydrogen fuel cell car, at a time when the government has stepped up measures to cut carbon emissions.