The Pentagon yesterday said it would be "a serious mistake" for Congress to follow the advice of the 46 senators who are demanding a big cut in President Reagan's request for the Strategic Defense Initiative (SDI), the "Star Wars" missile defense effort.

"The president has made it his highest priority," Defense Department spokesman Robert B. Sims said in launching the Pentagon's counterattack against the near majority of senators who last week called for no more than a 3 percent after-inflation increase for SDI over fiscal 1986.

Reagan is requesting a 77 percent fiscal 1987 increase, from $3 billion to $5.4 billion, counting money in the Energy Department budget for SDI.

Sims said Defense Secretary Caspar W. Weinberger will try to derail the effort to curb SDI research. The first test is likely to come next week when the Senate Armed Services Committee begins marking up the fiscal 1987 defense authorization bill, which will set a ceiling on how much can be appropriated.

The 46 senators expressed their objections to SDI in a letter to Armed Services Committee Chairman Barry Goldwater (R-Ariz.).

"It is difficult to conceive of a sound rationale for increasing the combined Department of Defense and Department of Energy SDI budget by 77 percent while the entire Department of Defense budget will be frozen at zero real growth and other vital military research programs are facing budget cuts," they wrote.

Sims said the cuts Congress made in SDI last year "have narrowed the range of technologies that we can explore. Further cuts would seriously compound the problems and set back the prospects for an informed decision in the early 1990s" on whether the research on the missile defense justified moving into full-scale development, he added.

The Pentagon, in trying to fend off deep cuts in SDI this year, faces an unusually broad coalition that has agreed to make scaling back SDI its main legislative objective in the defense field this year.

The alliance includes citizens' organizations like Common Cause, scientific groups and one-issue efforts like the National Campaign to Save the ABM Treaty.

Senators who signed the letter demanding the curbing of the Strategic Defense Initiative said their proposal appealed to both liberals and conservatives. Liberals who wanted no growth in the SDI budget went along with the 3 percent increase in the interest of scoring a victory against the Pentagon, while conservatives became convinced that slowing the missile defense effort would free money for conventional warfare accounts on the chopping block.